The evaluation of the SMAD1 rs1016792 polymorphism and gene expression on pulmonary hypertension due to congenital heart disease in children: a preliminary study.

Smad Family Member (SMAD), a protein family responsible for transducing the signal induced by TGF-ß into the nucleus, is thought to play a role in the pathology of many heart diseases. Therefore, we aimed to evaluate the influence of the SMAD1 rs1016792 polymorphism and gene expression on pulmonary arterial hypertension (PAH) due to congenital heart disease (CHD) in children. A total of 90 children, 45 of whom were PAH-CHD children and 45 healthy children, were included in the study. Patients were selected from those who were diagnosed and followed in the Department of Pediatric Cardiology.The SMAD1 rs1016792 genotyping and expression analysis was performed using a real-time polymerase chain reaction (RT-PCR)-based system. It was determined that the left ventricular end-diastolic diameter (LVEDD) value was lower in the patient group than in the control group, while the pulmonary artery pressure (PAP) value was higher in the patient group than in the control group. When the SMAD1 gene expression level was examined, a statistically significant difference was found between the patient and control groups. Patients had decreased SMAD1 expression compared to controls (p˂0.001). We found no significant difference between the patient and control groups in terms of SMAD1 rs1016792 genotype distribution or allele frequency (p > 0.05). There was no difference between genotype distribution and SMAD1 expression levels in the groups. In this study, we showed for the first time that SMAD1 expression is decreased in children with PAH-CHD. These results will be a preliminary step toward understanding the role of SMAD1 in the etiopathogenesis of CHD.

RhoA, ROCK-1, and ROCK-2 Gene Expression and Polymorphisms in Cholesteatoma Patients.

BACKGROUND: The aim of this study was to evaluate the gene polymorphism and expressions of Rho-A, ROCK-1, and ROCK-2 in cholesteatoma. METHODS: In this study, 120 healthy control group patients and 120 cholesteatoma patients were enrolled. Venous blood was taken from all of the cholesteatoma and control group patients. The genotyping of ROCK-1(G/T)rs35996865, ROCK-2(A/C)rs10178332, and Rho-A(A/T)rs2177268 polymorphisms was performed using predesigned TaqMan SNP Genotyping Assays. Assays-on-Demand SNP genotyping kit was used for the realtime polymerase chain reaction. The expression levels of Rho-A(Hs00357608_m1), ROCK-1(Hs01127699_m1), and ROCK-2(Hs00178154_m1) genes were determined. RESULTS: The expression of Rho-A, ROCK-1, and ROCK-2 was lower in cholesteatoma patients than in the control group. There was no difference in Rho-AAT/TT and ROCK-1GT/TT variation in cholesteatoma patients compared to the control. However, ROCK-2 AC/CC variance was lower in cholesteatoma patients. CONCLUSION: The expression of Rho-A, ROCK-1, and ROCK-2 genes may be decreased in cholesteatoma. Furthermore, since ROCK-2 AC/CC genotype is also lower in cholesteatoma, having C allele seems to decrease the risk of developing this disease.

[Investigation of the Relationship Between TNF-α, IL-12A, IL-12B and IFN-γ Gene Polymorphisms and Chronic Hepatitis C]. / TNF-α, IL-12A, IL-12B ve IFN-γ Gen Polimorfizmleri ile Kronik Hepatit C Arasindaki Iliskinin Arastirilmasi.

Hepatitis C virus (HCV) infection is still an important public health problem worldwide. Cytokines play an important role in the prognosis of HCV infections. Polymorphisms in the cytokine genes can affect the gene expression and change the clinical course of the disease. The aim of this study was to determine the relationship between chronic hepatitis C and TNF-α rs1799964 (-1031 T/C), IL-12A rs568408 (3'UTR G/A), IL-12B rs3212227 (3'UTR A/C) and IFN-γ rs2430561 (+874 A/T) gene polymorphisms. A hundred patients with chronic hepatitis C and 100 healthy people as control group were included in the study. Approximately 2 ml peripheral blood was taken from the patient and control groups into tubes with EDTA and genomic DNA was obtained using the DNA isolation kit. Single nucleotide polymorphisms in TNF-α (rs1799964), IL-12A (rs568408), IL-12B (rs3212227) and IFN-γ (rs2430561) genes were investigated by using the real-time polymerase chain reaction (Rt-PCR) method. The data obtained were analyzed in SPSS package program. There was no statistically significant relationship between chronic hepatitis C and TNF-α and IFN-γ polymorphisms in terms of genotype and allele distributions (p> 0.05). However, it was found that the relationship between IL-12A (G/A) and IL-12B (A/C) polymorphisms was significant (p< 0.05). The frequencies of IL-12A GA (OR= 4.828, 95% CI= 1.452-16.046, p= 0.010) and AA genotypes (OR= 4.436, 95% CI= 1.398-14.077, p= 0.011) and A alele (OR= 1.602, 95% CI= 1.020-2.518, p= 0.040) were found to be higher in the patient group. When the relationship between chronic hepatitis C and IL-12B gene polymorphism was examined, it was determined that the frequencies of AC (OR= 2.060, 95% CI= 0.836-5.076, p= 0.116) and CC (OR= 3.020, 95% CI= 1.242-7.345, p= 0.015) genotypes and C allele (OR= 1.750, 95% CI= 1.152-2.659, p= 0.008) were high in the patient group. In addition, TNF-α TC/CC, IL-12A GA/AA, IL-12B AC/CC and IFN-γ TT genotypes were found to be 7.5 times higher in the patient group than the control group (OR= 7.500, 95% CI= 1.532-36.714, p= 0.013). Our results showed that IL-12A (3'UTR G/A) and IL-12B (3'UTR A/C) gene polymorphisms and TNF-α TC/CC, IL-12A GA/AA, IL-12B AC/CC and IFN-γ TT interactions may be effective in the risk of the chronicity of hepatitis C. However, further studies are needed to determine the role of polymorphisms in these cytokine genes in HCV infections.